Toxic Optic Neuropathy

Optic nerve damage caused by exposure to drugs, chemicals, or environmental toxins, producing bilateral, symmetrical, painless central visual loss. Toxins damage retinal ganglion cell axons, particularly the papillomacular bundle, by mitochondrial dysfunction, oxidative stress, and demyelination.

• Drugs: ethambutol (dose and duration related, incidence about 1 percent at 15 mg/kg/day, 5 to 6 percent at 25 mg/kg/day, risk higher with renal impairment), linezolid (courses over 28 days), amiodarone, isoniazid, chloramphenicol, streptomycin, dapsone, vincristine, cisplatin, tacrolimus, ciclosporin, infliximab, tamoxifen, vigabatrin (peripheral field loss), disulfiram, and sildenafil (rare).
• Chemicals: methanol (formic acid), ethylene glycol, toluene and solvent inhalation, carbon monoxide, lead, mercury, thallium, organophosphates.
• Tobacco and alcohol (often together with nutritional deficiency): tobacco-alcohol amblyopia.
• Risk factors: renal or hepatic impairment, malnutrition, older age, diabetes, smoking and alcohol, and concomitant mitochondrial disease.

• Progressive, painless, bilateral and symmetric blurred vision and dyschromatopsia (red-green and blue-yellow errors), with centrocaecal or central scotomas; onset weeks to months after starting the drug.
• Normal or mildly hyperaemic discs early; later temporal pallor.
• Methanol: acute onset (12 to 24 hours) after ingestion of adulterated drink: headache, nausea, vomiting, abdominal pain, dyspnoea (metabolic acidosis), visual blurring or "snowfield" vision, dilated poorly reactive pupils, hyperaemic oedematous discs, then optic atrophy, with CNS depression and coma.
• Ethambutol: bilateral central loss or peripheral field loss (bitemporal), and may progress after cessation for 2 to 8 weeks (coasting).
• Amiodarone: insidious, disc swelling that persists for months and mimics non-arteritic ischaemic neuropathy.

• Drug and exposure history, dose and duration (weight-based dosing, renal function), alcohol and tobacco use, occupational and household exposures, and nutrition.
• Visual acuity, colour vision (Ishihara, Farnsworth D-15), visual fields (central 10-2 and 30-2 perimetry), pupils (relative afferent pupillary defect only if asymmetric), dilated fundus examination, and optical coherence tomography (retinal nerve fibre layer thickness).
• Visual evoked potentials (delayed or reduced) and electroretinogram to exclude retinal toxicity.
• MRI brain and orbits with contrast to exclude compressive and demyelinating disease; blood tests (vitamin B12, folate, copper, full count, liver and renal function, lactate, toxicology screen, serum methanol level, anion gap and osmolar gap, arterial blood gas).
• Genetic testing for mitochondrial mutations when the course is atypical.

• Stop the toxin as soon as the diagnosis is suspected: ethambutol, linezolid, amiodarone, and other agents should be stopped or replaced in consultation with the prescribing physician; recovery often begins within weeks to months (50 percent or more improve with prompt withdrawal).
• Methanol poisoning (emergency):
  • Fomepizole 15 mg/kg IV loading dose, then 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours until methanol level is below 20 mg/dL and the patient is asymptomatic with normal pH; alternatively ethanol infusion to maintain a blood ethanol of 100 to 150 mg/dL.
  • Folinic acid 1 mg/kg (50 mg) IV every 4 to 6 hours, or folic acid 50 mg IV every 4 hours.
  • Sodium bicarbonate 1 to 2 mEq/kg IV to correct pH above 7.3.
  • Haemodialysis for visual symptoms, severe acidosis, renal failure, or methanol level above 50 mg/dL.
• Ethambutol prevention: baseline visual acuity and colour vision, monthly acuity and colour vision testing for patients on more than 15 mg/kg or with renal impairment, dose adjustment, and informing the patient to stop and report any visual change.
• Nutritional support: hydroxocobalamin 1000 micrograms IM, thiamine 100 mg daily, folic acid 5 mg daily, multivitamins, and cessation of alcohol and tobacco.
• Linezolid: stop at the first sign, and avoid courses over 28 days if possible.
• Amiodarone: balance cardiac benefit with the risk to vision, consider alternatives.
• Low-vision rehabilitation and monitoring: acuity and fields every 1 to 3 months until recovery.